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Background: The “1-3-6-12-day rule” for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. Methods: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0–7), moderate (8–15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. Results: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)—initiating DOACS within 1, 2, 3, and 4 days, respectively—than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27–0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27–0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. Conclusions: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.

Background and Purpose: Evidence regarding sex differences in clinical outcomes and treatment effect following intracerebral hemorrhage is limited. Using the ATACH-2 trial (Antihypertensive Treatment in Intracerebral Hemorrhage-2) data, we explored whether sex disparities exist in outcomes and response to intensive blood pressure (BP)–lowering therapy. Methods: Eligible intracerebral hemorrhage subjects were randomly assigned to intensive (target systolic BP, 110–139 mm Hg) or standard (140–179 mm Hg) BP-lowering therapy within 4.5 hours after onset. Relative risk of death or disability corresponding to the modified Rankin Scale score of 4 to 6 was calculated, and interaction between sex and treatment was explored. Results: In total, 380 women and 620 men were included. Women were older, more prescribed antihypertensive drugs before onset, and had more lobar intracerebral hemorrhage than men. Hematoma expansion was observed less in women. After multivariable adjustment, the relative risk of death or disability in women was 1.19 (95% CI, 1.02–1.37, P =0.023). The relative risk of death or disability between intensive versus standard BP-lowering therapy was 0.91 (95% CI, 0.74–1.13) in women versus 1.13 (95% CI, 0.92–1.39) in men ( P for interaction=0.11), with inconclusive Gail-Simmon test ( P =0.16). Conclusions: Women had a higher risk of death or disability following intracerebral hemorrhage. The benefit of intensive BP-lowering therapy in women is inconclusive, consistent with the overall results of ATACH-2. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01176565.

Background: The present study aimed to clarify the association between left atrial (LA) size and ischemic events after ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF). Methods: Acute ischemic stroke or TIA patients with NVAF were enrolled. LA size was classified into normal LA size, mild LA enlargement (LAE), moderate LAE, and severe LAE. The ischemic event was defined as ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting, acute coronary syndrome or percutaneous coronary intervention, systemic embolism, aortic aneurysm rupture or dissection, peripheral artery disease requiring hospitalization, or venous thromboembolism. Results: A total of 1,043 patients (mean age, 78 years; 450 women) including 1,002 ischemic stroke and 41 TIA were analyzed. Of these, 351 patients (34%) had normal LA size, 298 (29%) had mild LAE, 198 (19%) had moderate LAE, and the remaining 196 (19%) had severe LAE. The median follow-up duration was 2.0 years (interquartile range, 0.9–2.1). During follow-up, 117 patients (11%) developed at least one ischemic event. The incidence rate of total ischemic events increased with increasing LA size. Severe LAE was independently associated with increased risk of ischemic events compared with normal LA size (multivariable-adjusted hazard ratio, 1.75; 95% confidence interval, 1.02–3.00). Conclusion: Severe LAE was associated with increased risk of ischemic events after ischemic stroke or TIA in patients with NVAF.

Background and Purpose: High blood pressure increases bleeding risk during treatment with antithrombotic medication. The association between blood pressure levels and the risk of recurrent stroke during long-term secondary stroke prevention with thienopyridines (particularly prasugrel) has not been well studied. Methods: This was a post hoc analysis of the randomized, double-blind, multicenter PRASTRO-I trial (Comparison of Prasugrel and Clopidogrel in Japanese Patients With Ischemic Stroke-I). Patients with noncardioembolic stroke were randomly assigned (1:1) to receive prasugrel 3.75 mg/day or clopidogrel 75 mg/day for 96 to 104 weeks. Risks of any ischemic or hemorrhagic stroke, combined ischemic events, and combined bleeding events were determined based on the mean level and visit-to-visit variability, including successive variation, of systolic blood pressure (SBP) throughout the observational period. These risks were also compared between quartiles of mean SBP level and successive variation of SBP. Results: A total of 3747 patients (age 62.1±8.5 years, 797 women), with a median average SBP level during the observational period of 132.5 mm Hg, were studied. All the risks of any stroke (146 events; hazard ratio, 1.318 [95% CI, 1.094–1.583] per 10-mm Hg increase), ischemic stroke (133 events, 1.219 [1.010–1.466]), hemorrhagic stroke (13 events, 3.247 [1.660–6.296]), ischemic events (142 events, 1.219 [1.020–1.466]), and bleeding events (47 events, 1.629 [1.172–2.261]) correlated with increasing mean SBP overall. Similarly, an increased risk of these events correlated with increasing successive variation of SBP (hazard ratio, 3.078 [95% CI, 2.220–4.225] per 10-mm Hg increase; 3.051 [2.179–4.262]; 3.276 [1.172–9.092]; 2.865 [2.042–4.011]; 2.764 [1.524–5.016], respectively). Event rates did not differ between the clopidogrel and prasugrel groups within each quartile of SBP or successive variation of SBP. Conclusions: Both high mean SBP level and high visit-to-visit variability in SBP were significantly associated with the risk of recurrent stroke during long-term medication with either prasugrel or clopidogrel after stroke. Control of hypertension would be important regardless of the type of antiplatelet drugs. Registration: URL: https://www.clinicaltrials.jp ; Unique identifier: JapicCTI-111582.

Background Various wearable devices for objectively evaluating motor symptoms of patients with Parkinson’s disease (PD) have been developed. Importantly, previous studies have suggested protective effects of physical activity in PD. However, the relationships between conventional clinical ratings for PD and three-axis accelerometer measures of physical activity (e.g., daily physical activity levels [PAL] or metabolic equivalents of task [METs]) are still unclear, particularly for METs. In the current study, we sought to elucidate these relationships on a daily basis, and to clarify optimal predictors for clinical states on a 30-min basis. Methods Patients who were hospitalized for adjustment of drugs or deep brain stimulation were enrolled. Using waist-worn three-axis accelerometers, PAL and METs parameter data were obtained and compared with UPDRS-3[On] and symptom diary data. We extracted data from the patients’ best and worst days, defined by the best and worst UPDRS-3[On] scores, respectively. Thus, 22 data sets from 11 patients were extracted. We examined the correlations and produced scatter plots to represent the relationships, then investigated which METs parameters and activity patterns were the best predictors for “On” and “dyskinesia”. Results The parameter “mean METs value within the 95–92.5 percentile range on a day (95–92.5 percentile value)” exhibited the strongest correlation with conventional daily clinical ratings (Rho: − 0.799 for UPDRS-3[On], 0.803 for On hours [p Conclusions This study suggested feasible activity patterns and METs parameters for objective evaluation of motor symptoms on a 30-min or daily basis. Three-axis accelerometer measures focusing on higher METs may be appropriate for evaluating physical activity. Further larger-scale studies are necessary to clarify the validity, reliability, and clinical utility of these objective measures.

Mutations in the valosin-containing protein (VCP) gene are known to cause various neurodegenerative disorders. Here, we report 8 Japanese patients [6 men, 2 women; median age at onset: 49.5 (range, 35–58) years] from 5 unrelated families with VCP missense mutations. Although 7 of 8 patients were diagnosed with either inclusion body myopathy or amyotrophic lateral sclerosis, 1 patient showed demyelinating polyneuropathy, which was confirmed by longitudinal nerve conduction studies. Sural nerve biopsy of the patient revealed intranuclear ubiquitin staining in Schwann cells. Three known pathogenic VCP mutations (p.Arg191Gln, p.Arg155Cys, and p.Ile126Phe) were detected. A novel mutation, c.293 A>T (p.Asp98Val), was also identified in a patient with amyotrophic lateral sclerosis and frontotemporal dementia. This mutation was predicted to be “deleterious” or “disease causing” using in silico mutation analyses. In conclusion, demyelinating polyneuropathy may be a novel phenotype caused by VCP mutations. The p.Asp98Val mutation was found to be a novel pathogenic mutation of VCP proteinopathy. We believe our cases represent a wide clinical spectrum of VCP mutations.

Background: Previous studies have revealed that hematoma growth mainly occurs during the first 6 h after the onset of spontaneous intracerebral hemorrhage (ICH). Early lowering of blood pressure (BP) may be beneficial for preventing hematoma growth. However, relationships between timing of BP lowering and hematoma growth in ICH remain unclear. We investigated associations between timing of BP lowering and hematoma growth for ICH. Methods: The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-ICH Study was a multicenter, prospective, observational study investigating the safety and feasibility of early (within 3 h from onset) reduction of systolic BP (SBP) to < 160 mm Hg with intravenous nicardipine for acute hypertension in cases of spontaneous ICH. The present study was a post hoc analysis of the SAMURAI-ICH study. We examined relationships between time from onset, imaging, and initiation of treatment to target SBP achievement and hematoma growth (absolute growth ≥6 mL) in ICH patients. Target SBP achievement was defined as the time at which SBP first became < 160 mm Hg. Results: Among 211 patients, hematoma growth was seen in 31 patients (14.7%). The time from imaging to target SBP and time from treatment to target SBP were significantly shorter in patients without hematoma growth than in those with (p = 0.043 and p = 0.032 respectively), whereas no significant difference was seen in time from onset to SBP < 160 mm Hg between groups (p = 0.177). Patients in the lower quartiles of time from imaging to target SBP and time from treatment to target SBP showed lower incidences of hematoma growth (p trend = 0.023 and 0.037 respectively). The lowest quartile of time from imaging to target SBP (< 38 min) was negatively associated with hematoma growth on multivariable logistic regression (OR 0.182; 95% CI 0.038–0.867; p = 0.032). Conclusions: Early achievement of target SBP < 160 mm Hg is associated with a lower risk of hematoma growth in ICH.

Background: We aimed to clarify associations between pre-admission risk scores (CHADS2, CHA2DS2-VASc, and HAS-BLED) and 2-year clinical outcomes in ischemic stroke or transient ischemic attack (TIA) patients with non-valvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry. Methods: From 18 Japanese stroke centers, ischemic stroke or TIA patients with NVAF hospitalized within 7 days after onset were enrolled. Outcome measures were defined as death/disability (modified Rankin Scale score ≥3) at 2 years, 2-year mortality, and ischemic or hemorrhagic events within 2 years. Results: A total of 1,192 patients with NVAF (527 women; mean age, 78 ± 10 years), including 1,141 ischemic stroke and 51 TIA, were analyzed. Rates of death/disability, mortality, and ischemic or hemorrhagic events increased significantly with increasing pre-admission CHADS2 (p for trend p for trend = 0.024 for events), CHA2DS2-VASc (p for trend p for trend = 0.004 for death/disability, p for trend p for trend = 0.024 for events) scores. Pre-admission CHADS2 (OR per 1 point, 1.52; 95% CI 1.35–1.71; p p p = 0.016 for events), CHA2DS2-VASc (1.55, 1.41–1.72, p < 0.001; 1.21, 1.12–1.30, p < 0.001; 1.17, 1.07–1.27, p < 0.001; respectively), and HAS-BLED (1.33, 1.17–1.52, p < 0.001; 1.23, 1.10–1.38, p < 0.001; 1.18, 1.05–1.34, p = 0.008; respectively) scores were independently associated with all outcome measures. Conclusions: In ischemic stroke or TIA patients with NVAF, all pre-admission risk scores were independently associated with death/disability at 2 years and 2-year mortality, as well as ischemic or hemorrhagic events within 2 years.

Objective:\ud It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed.\ud \ud Methods:\ud We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OACprior ) with those without prior oral anticoagulation (OACnaive ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OACchanged ) with those who continued the same anticoagulation as secondary prevention (OACunchanged ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).\ud \ud Results:\ud We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71-84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2-12]). The median CHA2 DS2 -Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OACprior (n = 1,195) and OACnaive (n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OACprior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OACchanged (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OACunchanged (n = 585).\ud \ud Interpretation:\ud Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA2 DS2 -Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group.

The epidemiology of patients with traumatic brain injury (TBI) has changed dramatically over recent decades as a result of rapid advances in aging societies. We assessed the influence of age on outcomes of patients with TBI and sought to identify prognostic factors for in-hospital mortality of TBI among elderly patients.Using a nationwide database, we analyzed data from 5651 patients with TBI. Univariate analysis was conducted to compare patient demographics, neurologic status on admission, radiologic findings, systemic complication rates, length of hospital stay, in-hospital mortality, and home discharge rates between elderly and nonelderly groups. Multivariable analysis was conducted to determine prognostic factors for in-hospital mortality among elderly patients.Overall in-hospital mortality was significantly higher in elderly patients (12.8% vs. 19.3%; P0.001). In-hospital mortality of elderly patients with mild TBI increased significantly at7 days after admission, whereas that of elderly patients with moderate or severe TBI was significantly higher immediately after admission. Age (odds ratio [OR], 1.62; P = 0.024), male sex (OR, 1.30; P = 0.004), Japan Coma Scale score on admission (OR, 5.95, P0.001), and incidence of acute subdural hematoma (OR, 1.89; P0.001) were associated with in-hospital mortality in elderly patients with TBI.Elderly patients with TBI showed significantly higher in-hospital mortality. Delayed increases in in-hospital mortality were observed among elderly patients with mild TBI. Level of consciousness on admission was the strongest predictor of in-hospital mortality among elderly patients.

Background Moyamoya vasculopathy (MMV) associated with Graves’ disease (GD) is a rare condition resulting in ischemic stroke accompanied by thyrotoxicity. Radiological findings of vasculitis have been reported in the walls of distal internal carotid arteries (ICAs) in these patients; however, no reports have described in detail the processes of progression of the lesions in the proximal ICA. Moreover, treatments to prevent recurrence of ischemic stroke and progression of MMV have not yet been sufficiently elucidated. Case presentation We report a progressive case of MMV associated with GD and review the literature to clarify relationships among recurrence, progression, thyrotoxicity and treatment. Our patient developed cerebral infarction during thyrotoxicity with no obvious stenosis of ICAs. Five months later, transient ischemic attacks recurred with thyrotoxicity. Antiplatelet therapy and intravenous methylprednisolone stopped the attacks. Stenosis of the left ICA from the proximal to distal portion and champagne bottle neck sign (CBN) were found. She declined any surgery. Afterward, gradual progression with mild thyrotoxicity was observed. Eventually, we found smooth, circumferential, concentric wall thickening with diffuse gadolinium enhancement of the left ICA from the proximal to the distal portion on T1-weighted imaging, suggesting vasculitis radiologically. The clinical and radiological similarities to Takayasu arteritis encouraged us to provide treatment as for vasculitis of medium-to-large vessels. In a euthyroid state and after administration of prednisolone and methotrexate, improved flow in the cerebrovascular arteries on magnetic resonance angiography was observed. Based on our review of the literature, all cases with recurrence or progression were treated with anti-thyroid medication (ATM) alone and accompanied by thyrotoxicity. CBN was observed in all previous cases for which images of the proximal ICA were available. Conclusions We report the details of progressive stenosis from a very early stage and radiological findings of vasculitis over the entire ICA in MMV associated with GD. Cerebral infarction can occur with no obvious stenosis of the ICA. We treated the patient as per vasculitis of a medium-to-large vessel. Management of GD by ATM alone seems risky in terms of recurrence. Adequate management of GD and possible vasculitis may be important for preventing recurrence and progression. Electronic supplementary material The online version of this article (10.1186/s12883-019-1262-1) contains supplementary material, which is available to authorized users.

Background Guillain-Barré syndrome (GBS), Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE) are a group of autoimmune neurological disorders (GBS spectrum disorder) that rarely recur. Recently, anti-ganglioside complex antibodies (GSC-Abs) were identified in patients with GBS spectrum disorder. However, there has been no case report describing GSC-Abs profiles in a recurrent case showing different phenotypes. Case presentation We report the case of a 33-year-old male patient with GQ1b-seronegative BBE-GBS after two prior episodes of MFS-GBS. Our patient showed ophthalmoplegia, ataxia, areflexia and a weakness of the extremities (MFS and GBS symptoms) in all episodes. In the episode reported here, our patient showed disturbed consciousness and an extensor response to cutaneous plantar stimulation was observed (BBE symptoms), with severe disability and requirement for artificial respiration management. GSC-Abs detected in previous episodes were also detected in the subsequent episodes, while new GSC-Abs emerged in each episode. Interestingly, whereas antibodies to GA1/GQ1b and GA1/GT1a, which are commonly identified in patients with GBS, MFS or BBE, appeared in all episodes, antibodies to GD1a/GD1b and GD1b/GT1b, which are predominantly associated with severe disability and the requirement for artificial respiration management in GBS, emerged for the first time in this episode. Conclusion This study reports novel phenomena about the GSC-Abs profiles and its relationship with clinical features in a case with recurrent GBS spectrum disorder, showing different phenotypes in different episodes. Further studies are required to reveal the significance of the GSC-Abs profiles in recurrent GBS spectrum disorder.

A 77-year-old man with a history of cigarette smoking had suffered from vertigo and depression repeatedly for twelve years. He gradually developed bradykinesia in the past half decade and fell down 3 times in the last half year. On admission, he presented with cerebellar ataxia and bulbar symptoms. Brain MRI showed atrophy in the cerebellum and brainstem. 123I-IMP SPECT showed hypoperfusion bilaterally in the cerebellum. Blood examinations showed various elevated inflammatory values and positive for HLA-B51. Cerebrospinal fluid (CSF) revealed aseptic meningitis and increased IL-6 levels. Therefore, we strongly suspected that he had chronic progressive neuro-Behcet's disease (CPNBD), clinically. Systemic mucocutaneous symptoms appeared 1 month after starting treatments. Pathological findings of his skin biopsy were consistent with Behcet's disease. It should be kept in mind that both positive HLA-B51 and increased CSF IL-6 levels have the possibility of containing important clues in the diagnosis of CPNBD.

Purpose Prognostic values of blood glucose levels following admission remain unclear. We investigated associations between blood glucose levels during the initial 72 h and outcomes of acute ICH. Methods Participants comprised hyperacute ICH patients who received intravenous antihypertensive treatment. Blood glucose levels were measured on admission and at 24 and 72 h after starting treatment, along with hemoglobin (Hb)A1c level on admission. Associations with clinical outcomes of hematoma expansion (> 33% increase), none to minimal disability (3-month modified Rankin Scale [mRS] 0–1) and bedridden or death (3-month mRS 5–6) were analyzed. Results Of the 176 patients (70 women; 65 ± 12 years), 30 (18%) showed hematoma expansion, and 33 (19%) had none to minimal disability and 15 (10%) were bedridden or died. On multivariate regression analysis, blood glucose at 24 h (per 10 mg/dl odds ratio [OR], 0.84; 95% confidence interval [CI], 0.69–0.98) and blood glucose at 72 h (OR, 0.75; 95%CI, 0.59–0.92) were inversely associated with none to minimal disability, and blood glucose at 24 h (OR, 1.14; 95%CI, 1.00–1.30) was positively associated with bedridden or death. No parameters were associated with hematoma expansion. Conclusions High blood glucose levels at 24 and 72 h were independently associated with poor functional outcomes 3 months after ICH. We need to investigate whether blood glucose control during the acute period ameliorates clinical outcomes.

Background: Little has been investigated about associations between timing of blood pressure lowering and clinical outcome of intracerebral hemorrhage (ICH). Methods: The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-ICH Study is a multicenter, prospective, observational study investigating the safety and feasibility of early (within 3 hours from symptom onset) systolic blood pressure (SBP) reduction to less than 160 mmHg with intravenous nicardipine for acute hypertension in patients with spontaneous ICH. We retrospectively examined the relationship between time from onset, CT imaging, and initiation of antihypertensive treatment to target SBP achievement and hematoma growth in ICH patients. Hematoma growth was defined as an absolute growth of ≥ 6 ml from baseline to second imaging at 24 (±6) hours after the initiation of antihypertensive treatment. Results: Among 211 patients (81 women (38.4%), mean age 66 years), mean baseline hematoma volume was 13 ml and hematoma growth was seen in 36 (17.1%) patients. Time from image to target SBP and time from treatment to target SBP were significantly shorter in patients without hematoma growth than those with ( P = 0.043 and P = 0.032, respectively), whereas there was not significant difference in time from onset to target SBP between the two groups ( P = 0.177). Lower quartiles of time from image to target SBP and time from treatment to target SBP had lower incidences of hematoma growth (P trend = 0.023 and 0.037, respectively, Cochran-Armitage test), whereas there was not significant trend in time from onset to target SBP ( P = 0.074). The lowest quartile of time from image to target SBP was negatively associated with hematoma growth on multivariate logistic regression (odds ratio 0.182, 95% confidential interval 0.038-0.867, P = 0.032). Conclusions: Early achievement to target SBP

Intravenous nicardipine is commonly used to reduce elevated blood pressure in acute intracerebral hemorrhage (ICH). We determined factors associated with nicardipine dosing and the association of dose with clinical outcomes in hyperacute ICH.Hyperacute (3 hours from onset) ICH patients with initial systolic blood pressure (SBP) greater than 180 mm Hg were included. All patients initially received 5 mg/hour of intravenous nicardipine. The dose was adjusted to maintain SBP between 120 and 160 mm Hg. Associations of maximum hourly and total doses with early neurologic deterioration (END), hematoma expansion (33%), and modified Rankin Scale score 4-6 at 3 months were assessed.Two hundred six patients (81 women, 65.8 ± 11.8 years) were studied. Initial SBP was 201.9 ± 15.9 mm Hg. Maximum and total nicardipine doses were 9.1 ± 4.2 mg/hour and 123.7 ± 100.2 mg/day, respectively. Multivariate analyses revealed that men (standardized regression coefficient [β] = .20, P = .0030 for maximum dose; β = .25, P = .0002 for total dose), age (β = -.28, P = .0002; β = -.25, P = .0005), and initial SBP (β = .19, P = .0018; β = .18, P = .0021) were independently associated with both maximum and total doses. Body weight (β = .20, P = .0084) was independently associated with total dose. After multivariate adjustment, maximum dose (per 1 mg/hour; odds ratio [OR], 1.25; 95% confidence interval [CI], 1.09-1.45) was independently, and total dose (per 10 mg/day; OR, 1.06; 95% CI, .998-1.132) tended to be independently, associated with END. Nicardipine dose was not associated with hematoma expansion or 3-month outcome.Nicardipine dose is roughly predictable with sex, age, body weight, and initial SBP in acute ICH. The maximum dose was associated with neurologic deterioration.

Background and purpose The characteristics of reverse magnetic resonance angiography and diffusion-weighted imaging (MRA-DWI) mismatch (RMM), defined as a large DWI lesion in the absence of major artery occlusion (MAO), remain unknown, especially in patients treated with intravenous recombinant tissue plasminogen activator (rt-PA). Methods Patients with stroke in the middle cerebral artery territory were included. Early ischaemic changes (EIC) were assessed with the Alberta Stroke Program Early CT Score on DWI (DWI-ASPECTS). All patients were divided into four groups based on the presence of MAO and a DWI-ASPECTS cut-off value of

Background The therapeutic efficacy of low-dose intravenous alteplase (0.6 mg/kg) for basilar artery occlusion (BAO) remains unknown. Methods BAO patients enrolled from the Japanese multicenter registry involving 600 stroke patients treated with the low-dose intravenous alteplase were studied. Results Twenty-five patients had BAO (8 women ranging from 32-92 years of age; mean baseline National Institutes of Health Stroke Scale [NIHSS] score 16). The stroke subtype was cardioembolic in 15 patients and atherothrombotic in 4 patients. BAO was recanalized during hospitalization in 18 (78%) of 23 patients undergoing follow-up angiography. Within the initial 24 hours, 14 patients (56%) had a ≥8-point decrease in the NIHSS score, being more common than 267 patients with middle cerebral artery occlusion (MCO) from the same registry (odds ratio [OR] 2.50; 95% confidence interval [CI] 1.06-5.97) after adjustment by sex, age, and baseline NIHSS score. In addition, 4 patients (16%) had a ≥4-point increase in the score, being marginally more common than MCO patients (OR 3.13; 95% CI 0.81-10.25). Symptomatic intracranial hemorrhage within the initial 36 hours (8% v 5%), independence at 3 months (modified Rankin Scale score ≤2, 48% v 52%), and mortality at 3 months (4% v 6%) were similar when comparing BAO and MCO patients. When compared with previous studies of BAO, vital and functional outcomes at 3 months were relatively better in our study. Conclusions The use of low-dose alteplase resulted in similar outcomes when comparing acute BAO and MCO patients.

Background We aimed to devise a scale comprising a simple multiplication of initial National Institutes of Health Stroke Scale (NIHSS) score and onset-to-treatment time (OTT) as a scale for predicting outcomes after recombinant tissue plasminogen activator (rt-PA) therapy. Methods Data from rt-PA patients in 10 stroke centers in Japan were investigated. NIHSS-time score was calculated as initial NIHSS score × OTT. Results Subjects comprised 526 patients. Median NIHSS score was 12 (7–18), and median OTT was 2.42 h (2.00–2.75 h). Median NIHSS-time score was 27.7 (16.9–41.7). Good (modified Rankin Scale [mRS] 0–1) and poor (mRS 4–6) outcome rates at 3 months for patients with NIHSS-time scores ≤ 10 were 71.1% and 7.8%, compared to 54.7% and 16.5% for scores > 10 and ≤ 20, 38.9% and 31.9% for scores > 20 and ≤ 30, 25.0% and 44.6% for scores > 30 and ≤ 40, and 17.4% and 61.8% for scores > 40, respectively. Cut-off NIHSS-time scores to predict good and poor outcomes with 50% probability were defined as 20 and 40, respectively. Multivariate logistic regression analysis revealed NIHSS-time score as an independent predictor of good (odds ratio [OR], 0.587; 95% confidence interval [CI], 0.422–0.818, p = 0.002) and poor (OR, 1.756; 95%CI, 1.227–2.514, p = 0.002) outcomes after adjusting for age, sex, NIHSS score, OTT, Alberta Stroke Program Early CT Score, internal carotid artery occlusion, and glucose level. Conclusions NIHSS-time score predicts clinical outcomes in rt-PA patients.

Background and Purpose— The discrimination between paroxysmal and sustained (persistent or permanent) atrial fibrillation (AF) has not been considered in the approach to secondary stroke prevention. We aimed to assess the differences in clinical outcomes between mostly anticoagulated patients with sustained and paroxysmal AF who had previous ischemic stroke or transient ischemic attack. Methods— Using data from 1192 nonvalvular AF patients with acute ischemic stroke or transient ischemic attack who were registered in the SAMURAI-NVAF study (Stroke Management With Urgent Risk-Factor Assessment and Improvement-Nonvalvular AF; a prospective, multicenter, observational study), we divided patients into those with paroxysmal AF and those with sustained AF. We compared clinical outcomes between the 2 groups. Results— The median follow-up period was 1.8 (interquartile range, 0.93–2.0) years. Of the 1192 patients, 758 (336 women; 77.9±9.9 years old) and 434 (191 women; 77.3±10.0 years old) were assigned to the sustained AF group and paroxysmal AF groups, respectively. After adjusting for sex, age, previous anticoagulation, and initial National Institutes of Health Stroke Scale score, sustained AF was negatively associated with 3-month independence (multivariable-adjusted odds ratio, 0.61; 95% confidence interval, 0.43–0.87; P =0.006). The annual rate of stroke or systemic embolism was 8.3 and 4.6 per 100 person-years, respectively (multivariable-adjusted hazard ratio, 1.95; 95% confidence interval, 1.26–3.14) and that of major bleeding events was 3.4 and 3.1, respectively (hazard ratio, 1.13; 95% confidence interval, 0.63–2.08). Conclusions— Among patients with previous ischemic stroke or transient ischemic attack, those with sustained AF had a higher risk of stroke or systemic embolism compared with those with paroxysmal AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01581502.

Background and purpose: The discrimination between paroxysmal and persistent atrial fibrillations (AF) has not been considered to guide secondary stroke prevention, because it remains unclear whether patients with persistent AF are at higher risk compared with paroxysmal AF, particularly in secondary prevention. We aimed to assess the differences in clinical outcomes between mostly anticoagulated patients with persistent vs. paroxysmal AF who had ischemic stroke or TIA. Methods: Using interim data of 1192 nonvalvular AF (NVAF) patients with acute ischemic stroke or TIA who were registered in the SAMURAI-NVAF study (an ongoing prospective, multicenter, observational study) to determine choice of anticoagulantion therapy and clinical outcomes, we divided patients into those with paroxysmal AF and those with persistent AF. We compared clinical outcomes between the 2 groups. Results: The median follow-up period was 1.0 year (IQR 0.3-2.0). Of the 1192 patients, 434 (191 women, 77.3±10.0 y.o.) and 758 (336, 77.9±9.9) were assigned to the paroxysmal AF group and persistent AF group, respectively. Of each group, 220 (50.7%) and 442 (58.3%) were anticoagulated with warfarin and 199 (45.9%) and 276 (36.4%) were so with non-vitamin K antagonist oral anticoagulant (NOAC) (p=0.004). As for primary outcomes, 30 (6.2%/person-year) and 78 (9.9) ischemic events, respectively [hazard ratio adjusted for sex, age, initial NIHSS, CHADS2 score, creatinine clearance, anticoagulation with warfarin (vs. NOAC) (HR) 0.65; 95% CI 0.42-0.98], and 18 (4.9%/person-year) and 31 (3.8) hemorrhagic events, respectively (HR 0.97, 0.52-1.75), occurred during follow-up. As for secondary outcomes, the person-year rate of ischemic stroke or TIA was 3.9% and 8.4%, respectively (HR 0.46, 0.27-0.76), that of intracranial hemorrhage was 1.6% and 1.7%, respectively (HR 0.97, 0.36-2.37), and that of death was 11.1% and 15.7%, respectively (HR 0.90, 0.64-1.26). Conclusions: Among patients with prior ischemic stroke or TIA, those with persistent AF had a higher risk of ischemic events, and ischemic stroke or TIA compared with those with paroxysmal AF. The prevention of progress to persistent AF from paroxysmal AF may be beneficial for secondary prevention in patients with NVAF.

Objective: The intracardiac thrombus is associated with an increase in the risks of stroke and thromboembolism for primary prevention. However, it remains unclear in the setting of early management of patients with acute ischemic stroke/TIA. The purpose of this study was to clarify the impact of intracardiac thrombi on recurrent ischemic events in acute ischemic stroke/TIA patients with nonvalvular atrial fibrillation (NVAF). Methods: In the SAMURAI-NVAF study (an ongoing prospective, multicenter, observational study), 1192 acute ischemic stroke/TIA patients with NVAF were registered. Of these, the patients who underwent transesophageal echocardiography (TEE) and/or transthoracic echocardiography (TTE) during acute hospitalization were included. We evaluated the association between the prevalence of intracardiac thrombi and recurrent ischemic events (composite of ischemic stroke/TIA and systemic embolism) during hospital stay (median 29 days). Results: A total of 1091 patients (474 women, 77.6±9.9 y.o) were studied. Of these, 48 patients had intracardiac thrombus (4.4% [95% CI, 3.3-5.7%]). In acute hospital stay, 29 recurrent ischemic events (2.7% [1.9-3.8%]; 24 ischemic stroke, 3 TIA, and 2 systemic embolism) occurred. Patients with intracardiac thrombi had higher incidence of recurrent ischemic events than those without (12.5% versus 2.2%, p Conclusion: In acute ischemic stroke/TIA patients with NVAF, intracardiac thrombi are associated with risk of recurrent ischemic events. The evaluation of intracardiac thrombus should be considered in acute phase of ischemic stroke/TIA.

Background: The effects of lipid levels on clinical outcomes after ischemic stroke are controversial. Whether admission lipid levels and prior statin use are associated with early intracerebral hemorrhage (ICH) and long-term functional outcome after recombinant tissue plasminogen activator (rt-PA) therapy for stroke patients was investigated. Methods: Ischemic stroke patients who received intravenous rt-PA from a multicenter registry were studied. Lipid levels on admission, including total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and triglyceride levels, as well as prior statin use, were assessed. The primary outcome was favorable outcome at 3 months corresponding to a modified Rankin Scale score ≤1. The secondary outcome was any or symptomatic ICH within the initial 36 h. Results: Of 489 enrolled patients (171 women, 70.8 ± 11.6 years old), 60 used statins prior to stroke, 93 developed ICH (19.0%), and 188 (38.4%) had a favorable 3-month outcome. Of the lipid levels, only the HDL-C level was an independent predictor of favorable outcome after multivariate adjustment for baseline characteristics (OR 1.95, 95% CI 1.10–3.47 per 1 mmol/l; p = 0.023) and after further adjustment for pretreatment radiological findings (OR 2.03, 95% CI 1.07–3.84; p = 0.029). For the 187 stroke patients without cardioembolism, the HDL-C level was more strongly associated with favorable outcome (OR 4.94, 95% CI 1.91–12.76 per 1 mmol/l; p = 0.001). There were no significant associations between ICH and any lipid levels. Prior statin use was not associated with outcomes. Conclusions: The admission HDL-C level was associated with favorable outcome 3 months after intravenous rt-PA therapy in stroke patients without cardioembolism.

Purpose A nationwide survey was conducted regarding anticoagulant therapy in patients with acute intracerebral hemorrhage (ICH) on warfarin with nonvalvular atrial fibrillation (NVAF). Methods A questionnaire on standard therapeutic strategy for warfarin-related ICH in patients with NVAF was mailed to 416 institutes. Results A total of 329 physicians (79%) responded with a completed questionnaire. On admission, all respondents stopped warfarin medication and 94% normalized the international normalized ratio (INR) mainly by Vitamin K (63%), followed by fresh frozen plasma (20%), and prothrombin complex concentrate (10%). Afterwards, 91% of the respondents restarted anticoagulation and 3% used antiplatelet for prevention of thromboembolism, but the remaining 6% disagreed with restarting antithrombotic therapy. As contraindications for resuming anticoagulation, recurrent ICH (59%) and poor functional condition (59%) were often chosen. Of those who restarted anticoagulation, the timing was within 4 days in 7%, 5 to 7 days in 21%, 8 to 14 days in 25%, 15 to 28 days in 28% and 29 days or later in 18%. The major key finding on follow-up CT to restart anticoagulation was the absorption tendency of hematomas (47%). When restarting anticoagulation, 76% of the respondents used warfarin alone and 20% used either unfractionated heparin plus warfarin or heparin alone. Conclusion A large majority of respondents responsible for ICH management stopped oral warfarin medication and normalized INR on admission, and restarted anticoagulation after acute ICH in patients with NVAF. However, the strategies to normalize INR and to restart anticoagulant therapy varied greatly and depended on each individual physician's decision.

Background: The initial 24 h after thrombolysis are critical for patients’ conditions, and continuous neurological assessment and blood pressure measurement are required during this time. The goal of this study was to identify the clinical factors associated with early neurological deterioration (END) within 24 h of stroke patients receiving intravenous recombinant tissue plasminogen activator (rt-PA) therapy and to clarify the effect of END on 3-month outcomes. Methods: A retrospective, multicenter, observational study was conducted in 10 stroke centers in Japan. A total of 566 consecutive stroke patients [211 women, 72 ± 12 years old, the median initial NIH Stroke Scale (NIHSS) score of 13] treated with intravenous rt-PA (0.6 mg/kg alteplase) was studied. END was defined as a 4-point or greater increase in the NIHSS score at 24 h from the NIHSS score just before thrombolysis. Results: END was present in 56 patients (9.9%, 18 women, 72 ± 10 years old) and was independently associated with higher blood glucose [odds ratio (OR) 1.17, 95% confidence intervals (CI) 1.07–1.28 per 1 mmol/l increase, p < 0.001], lower initial NIHSS score (OR 0.92, 95% CI 0.87–0.97 per 1-point increase, p = 0.002), and internal carotid artery (ICA) occlusion (OR 5.36, 95% CI 2.60–11.09, p < 0.001) on multivariate analysis. Symptomatic intracranial hemorrhage within the initial 36 h from thrombolysis was more common in patients with END than in the other patients (per NINDS/Cochrane protocol, OR 10.75, 95% CI 4.33–26.85, p < 0.001, and per SITS-MOST protocol, OR 12.90, 95% CI 2.76–67.41, p = 0.002). At 3 months, no patients with END had a modified Rankin Scale (mRS) score of 0–1. END was independently associated with death and dependency (mRS 3–6, OR 20.44, 95% CI 6.96–76.93, p < 0.001), as well as death (OR 19.43, 95% CI 7.75–51.44, p < 0.001), at 3 months. Conclusions: Hyperglycemia, lower baseline NIHSS score, and ICA occlusion were independently associated with END after rt-PA therapy. END was independently associated with poor 3-month stroke outcome after rt-PA therapy.

Background and Purpose— Alberta Stroke Programme Early CT Score (ASPECTS) is a quantitative topographical score to evaluate early ischemic change in the middle cerebral arterial territory on CT as well as on diffusion-weighted imaging (DWI). The aim of the present study was to elucidate the relationship between CT-ASPECTS and DWI-ASPECTS for patients with hyperacute stroke and their associations with outcomes after recombinant tissue-type plasminogen activator therapy based on a multicenter registry. Methods— ASPECTS was assessed on both CT and DWI before intravenous 0.6 mg/kg alteplase in 360 patients with stroke (119 women, 71±11 years old). The outcomes were symptomatic intracerebral hemorrhage within 36 hours and independence at 3 months defined by a modified Rankin Scale score of 0 to 2. Results— DWI-ASPECTS was positively correlated with CT-ASPECTS (ρ=0.511, P P P P P =0.275). The area for predicting independence at 3 months (192 patients) was 0.621 (0.564 to 0.674) by CT and 0.639 (0.580 to 0.694) by DWI ( P =0.535). Conclusions— For patients with hyperacute stroke, DWI-ASPECTS scored approximately 1 point lower than CT-ASPECTS. Both CT-ASPECTS and DWI-ASPECTS were useful predictors of symptomatic intracerebral hemorrhage and independence at 3 months after recombinant tissue-type plasminogen activator.

To evaluate whether the pretreatment Alberta Stroke Programme Early CT Score (ASPECTS) assessed using diffusion-weighted imaging (DWI) predicts stroke outcomes at 3 months following IV recombinant tissue-type plasminogen activator (rt-PA) therapy.Stroke patients treated with rt-PA (0.6 mg/kg alteplase) in 10 stroke centers in Japan were retrospectively studied. ASPECTS was assessed on DWI just prior to rt-PA injection. The primary outcome was a modified Rankin Scale (mRS) score of 0-2 at 3 months. Secondary outcomes included death at 3 months and symptomatic intracerebral hemorrhage (sICH) within 36 hours.For the 477 patients (316 men, 71 +/- 11 years old) enrolled, the median NIH Stroke Scale score was 13 (interquartile range 7-18.5), the median ASPECTS on DWI was 8 (7-10), and sICH was identified in 15 patients (3.1%). At 3 months, 245 (51.4%) had an mRS score of 0-2, and 29 (6.1%) had died. Patients with an mRS score of 0-2 had higher median ASPECTS (9; interquartile range 8-10) than other patients (8; 6-9, p0.001). Using receiver operating characteristic curves, the optimal cutoff ASPECTS to predict an mRS score of 0-2 wasor =7. On multivariate regression analysis, ASPECTSor =7 was related to an mRS score of 0-2 (odds ratio 1.85; 95% confidence interval 1.07-3.24), ASPECTSor =4 was related to death (3.61; 1.23-9.91), and ASPECTSor =5 was related to sICH (4.74; 1.54-13.64).ASPECTS on DWI was independently predictive of functional and vital outcomes at 3 months, as well as sICH within 36 hours, following rt-PA therapy for stroke patients.

Background Because patients with warfarin-associated intracerebral hemorrhage (WAICH) have a high risk of ongoing bleeding, disability, and death, urgent coagulopathy reversal should be considered. On the other hand, thromboembolism may occur with reversal or withholding of anticoagulant therapy. The current status of acute hemostatic treatments and clinical outcomes in WAICH patients was investigated. Methods WAICH patients admitted within 3 days of onset were prospectively enrolled in 10 stroke centers. Thromboembolic and hemorrhagic complications and functional outcomes were followed-up for one year. Results Of 50 WAICH patients (31 men, 73 ± 9 years old) enrolled, all stopped warfarin on admission. Elevated prothrombin time-international normalized ratios (PT-INR) were normalized in 43 (86%). Anticoagulant therapy was resumed with intravenous full-dose unfractionated heparin followed by warfarin in 9 (18%), intravenous low-dose unfractionated heparin followed by warfarin in 14 (28%) and warfarin alone in 14 (28%) at a median of 2.5 (IQR 1.25–9), 4 (2–5.5) and 6 (3–11) days after onset, respectively, after emergent admission. Onset-to-admission time (per 1-hour increase; OR 0.55, 95% CI 0.19–0.84) was inversely associated with hematoma expansion. Anticoagulant therapy was resumed with intravenous full-dose unfractionated heparin in 9 (18%), low-dose heparin in 14 (28%) and warfarin alone in 14 (28%) at a median of 2.5, 4 and 6 days after onset, respectively. During one-year follow-up (n = 47), 11 thromboembolic and 6 hemorrhagic complications were documented. Twenty four patients showed unfavorable outcomes, corresponding to a modified Rankin Scale score of 4–6. Thromboembolic complications (OR, 10.62; 95% CI, 1.05–227.85), as well as advanced age (per 1 year; OR, 1.27; 95% CI, 1.10–1.61) and higher National Institutes of Health Stroke Scale (NIHSS) score (per 1 point; OR, 1.24; 95% CI 1.07–1.55), were independently associated with unfavorable outcome. Conclusions PT-INR normalization on admission and early anticoagulant resumption were common in WAICH patients. Thromboembolic complications were independently associated with unfavorable outcome.

Backgound and Purpose: Recently, three non-vitamin K antagonist oral anticoagulants (NOACs) became available for patients with nonvalvular atrial fibrillation (NVAF) in Japan. We aimed to determine 3-month outcomes in ischemic stroke/TIA patients receiving NOACs or warfarin from a multicenter prospective registry (SAMURAI-NVAF registry, NCT01581502). Methods: Among 1,191 acute ischemic stroke /TIA patients enrolled between September 2011 and March 2014, we studied 916 patients (389 women, 77±10 y) who took oral anticoagulants (OACs) after index stroke and completed 3-month follow-up survey. Primary outcome measures were ischemic events, including recurrent stroke/TIA and thromboembolism, and major bleedings events, such as fatal bleeding and/or symptomatic bleeding in a critical area or organ according to the International Society on Thrombosis and Haemostasis statement. We assessed the incidence and clinical factors associated with primary outcomes within 90 days after initiating OACs. Results: NOACs were given for 370 patients (126 women, 74±9 y; dabigatran 168, rivaroxaban 183 and apixaban 19) and warfarin for 546 (263 women, 79±10 y). NOAC users had lower scores of CHADS2 (median 3 in NOAC, 4 in warfarin, p Conclusion: The 3-month incidence of ischemic events in stroke/TIA patients with NVAF was approximately 4% in both NOAC and warfarin users. Intracranial hemorrhage was relatively infrequent in NOAC users.

Background and Purpose: We aimed to assess whether prior antithrombotic therapy affects initial neurological severity and functional outcome in acute ischemic stroke patients with non-valvular atrial fibrillation (NVAF). Methods: Patients with NVAF who were admitted within 7 days after ischemic stroke onset from 2011 to 2014 were enrolled from the register of a prospective, multicenter, observational study (the SAMURAI-NVAF study). Patients receiving novel oral anticoagulants at onset were excluded from the study. They were classified into 3 groups: the non-WF group, patients without prior warfarin; the iWF group, those on warfarin with initial PT-INR below the target range; the sWF group, those on warfarin with initial PT-INR within or above the target range. They were also divided into patients without prior antiplatelet agents (the non-AP group) and those with (the AP group). Initial neurological severity was measured by NIHSS score. Poor functional outcome was defined by mRS 3-6 at 3 months of onset. Results: Of 1000 patients studied, 713, 221 and 66 were assigned to the non-WF group, the iWF group and the sWF group, respectively. Of all, 245 were assigned to the AP group, mainly taking aspirin (202 patients). On multivariate analysis, the sWF group (vs. the non-WF group) (standardized regression coefficient [β], -0.23; p Conclusions: Prior sufficient warfarinization was associated with mild neurological severity and favorable outcome in acute ischemic stroke patients with NVAF, whereas prior insufficient warfarinization and prior antiplatelet therapy were not.

Background and purpose: Although low serum total cholesterol (TC) levels are associated with an increased risk of intracerebral hemorrhage (ICH), the prognostic value of lipid parameters is not fully known. We aimed to determine the association between lipid parameters on admission and clinical outcomes in acute ICH patients. Methods: This study is a post-hoc analysis of the SAMURAI-ICH study, which was a prospective, multicenter, observational study. Hyperacute (hospitalized 33% increase), neurological deterioration (a decrease of ≥2 in GCS or an increase of ≥4 in NIHSS from baseline to 72 hours), favorable outcome (3-month mRS 0-2) and unfavorable outcome (3-month mRS 4-6). Results: Of the 204 patients (78 women; 66±12 years; median baseline NIHSS, 13 [8-17]), a statin was prescribed in 16 (8%). Of all, 35 (17%) showed hematoma expansion, 16 (8%) experienced neurological deterioration, and 80 (of 199 with premorbid mRS 0-2, 40%) and 84 (41%) had favorable and unfavorable outcomes, respectively. Levels of TC, TG, HDLC and LDLC were 196±40, 125±69, 59±17and 112±34mg/dl, respectively. On multivariate regression analyses adjusted for established prognostic predictors, TG (odds ratio per 10mg/dl [OR], 1.06; 95% confidence interval [CI], 1.002-1.13; p=0.042) was associated with hematoma expansion, and HDLC (OR, 1.30; 95% CI, 1.04-1.65; p=0.024) was positively, and LDLC (OR, 0.89; 95% CI, 0.80-0.999; p=0.048) was inversely associated with favorable outcome. Although prior statin use was not associated with any clinical outcomes, HDLC (OR, 1.20; 95% CI, 0.95-1.53; p=0.123) and LDLC (OR, 0.90; 95% CI, 0.79-1.01; p=0.071) were no more significantly associated with favorable outcome after excluding patients with prior statin. No parameters were significantly associated with neurological deterioration and unfavorable outcome. Conclusions: High TG level was associated with hematoma expansion. High HDLC and low LDLC levels were associated with independence at 3 months after onset in patients with acute ICH.

Background and purpose: The impact of albuminuria on clinical outcomes in acute cardioembolic stroke is not fully investigated. We assessed whether high spot urine albumin/creatinine ratio (ACR) was associated with clinical outcomes in acute stroke with non-valvular atrial fibrillation (NVAF). Methods: From 2011 to 2014, we enrolled acute ischemic stroke/TIA patients with NVAF in the SAMURAI-NVAF study, which is a multicenter, observational study. Patients with complete ACR values were included in the analysis. They were divided into the N (normal, ACR < 30mg/g) and the H (high, ACR ≥ 30mg/g) groups. Clinical outcomes were neurological deterioration (an increase of NIHSS ≥1 point during the initial 7 days) and poor outcome (mRS of 4-6 at 3 months). Results: Of 558 patients (328 men, 77±10 y) who were included, 271 and 287 were assigned to the H group and the N group, respectively. As compared with patients in the N group, those in the H group were more frequently female (52 vs 31%, p < 0.001) and older (80±10 vs 75±10 y, p < 0.001). On admission, patients in the H group more frequently had diabetes (28 vs 17%, p = 0.003), less frequently had paroxysmal AF (68 vs 57%, p = 0.009), had higher levels of SBP (157±28 vs 151±24 mmHg, p = 0.003), NIHSS score (11 vs 5, p < 0.001), CHA2DS2-VASc score (6 vs 5, p < 0.001), plasma glucose (141±62 vs 132±41 mg/dL, p = 0.04), and brain natriuretic peptide (348±331 vs 259±309 pg/mL, p = 0.002), and had lower levels of hemoglobin (13±2 vs 14±2 g/dL, p = 0.02), and estimated glomerular filtration ratio (eGFR) (60±24 vs 66±20 mL/min/1.73m2 p = 0.002). On imaging studies, patients in the H group more frequently had large infarct (29 vs 20 %, p = 0.02) and culprit artery occlusion (64 vs 48%, p < 0.001). Neurological deterioration (14 vs 4%, p < 0.001) and poor outcome (49 vs 24%, p < 0.001) were more frequently observed in the H group. On multivariate regression analysis adjusted for significant confounders and reperfusion therapy, the H group was associated with neurological deterioration (OR 2.43; 95% CI 1.14-5.5; p = 0.02) and poor outcome (OR 2.75; 95% CI 1.45-5.2; p = 0.002), although eGFR was not significantly related to either. Conclusion: High ACR, a marker of albuminuria, was independently associated with unfavorable outcomes in acute stroke patients with NVAF.

Background and Purpose: In almost all acute stroke units in Japan, staffing level is lower on weekends and holidays and rehabilitative services are provided only on weekdays. We sought to investigate the effects of low-volume care early after stroke resulting from weekends and holidays on the outcome of stroke. Methods: Patients with completed stroke within 72 h of onset were prospectively registered by 10 acute stroke units in Japan. Main outcome measures were favorable outcomes as indicated by a score of 0–1 on the modified Rankin scale (mRS01) on their 21st hospital day and at discharge and case fatality during the hospital stay. Cox proportional hazardsmodels were used to identify the effects of weekday admission and a weekday ratio (a number of weekdays / total length of hospital stay, or 21 days if hospitalization was longer than 21 days) on the main outcome measures. Results: In a total of 1,134 patients, Cox proportional hazards regression analyses demonstrated that the weekday admission was significantly associated with mRS01 at discharge (hazard ratio, HR: 1.385, 95% CI: 1.087–1.764) and case fatality (HR: 0.477, 95% CI: 0.285–0.798). In 858 patients with rehabilitative therapy, the weekday ratio was significantly associated with mRS01 at discharge (p = 0.014). Compared with the lowest tertile of weekday ratio (71.4%) was significantly positively associated with mRS01 at discharge (HR: 1.524, 95% CI: 1.053–2.206; p < 0.026). Conclusions: Weekday admission was an independent negative predictor of case fatality and a positive predictor of favorable outcome (mRS01) at discharge from acute stroke units. In patients with rehabilitative therapy, a reduction in the weekday ratio was also associated with unfavorable outcome, probably due to a reduction in multidisciplinary care.

Background and Purpose— The purpose of this study was to determine the safety and efficacy of intravenous recombinant tissue-type plasminogen activator (0.6 mg/kg alteplase) within 3 hours of stroke onset in Japanese patients outside the indications in the European license. Methods— Of the 600 patients who were treated with recombinant tissue-type plasminogen activator, 422 met the inclusion criteria of the European license (IN group) and 178 did not (OUT group). Results— The OUT group was inversely associated with any intracerebral hemorrhage (adjusted OR, 0.50; 95% CI, 0.29–0.84), positively associated with an unfavorable outcome (2.48; 1.55–3.94) and mortality (2.04; 1.02–4.04), and not associated with symptomatic intracerebral hemorrhage (0.53; 0.11–1.79) or complete independency (0.65; 0.40–1.03) after multivariate adjustment. Conclusions— Functional and vital outcomes 3 months after low-dose recombinant tissue-type plasminogen activator in patients outside the European indications were less favorable compared with those included in the indications; however, the risk of intracerebral hemorrhage was not.

The effect of renal dysfunction on intracerebral hemorrhage (ICH) remains unclear. We investigated associations of renal dysfunction assessed by estimated glomerular filtration rate (eGFR) with clinical courses and outcomes in ICH patients.From a prospective, multicenter, observational study, 203 patients who had supratentorial ICH within 3 hours of onset were included. Patients were classified into 3 groups based on eGFR: Group 1 (eGFR60 mL/minute/m(2)), Group 2 (60-89), and Group 3 (≥ 90). Outcomes included neurologic deterioration within 72 hours, hematoma expansion (33% in volume) at 24 hours, and favorable (modified Rankin Scale [mRS] ≤ 2) or unfavorable (mRS ≥ 5) outcome at 3 months.Thirty-seven patients (16 women, 74.6 ± 13.2 years) were assigned to Group 1, 99 (34 women, 65.2 ± 11.4 years) to Group 2, and 67 (30 women, 61.3 ± 9.4 years) to Group 3. Significant differences were found in age (P.001) and initial systolic blood pressure among the groups (208.4 ± 18.0, 201.9 ± 15.1, and 198.1 ± 14.2 mm Hg for Group 1, 2, and 3, respectively; P = .006). Similar rates of neurologic deterioration (14%, 6%, and 6%) and hematoma expansion (16%, 14%, and 18%) were observed among the groups. However, in Group 1, favorable outcome was less frequent (17%, 48%, and 42%; P = .002) and unfavorable outcome was more frequent (24%, 7%, and 6%; P = .013) than in the other groups. After adjustment for confounders, eGFR60 mL/minute/m(2) was independently associated with both favorable outcome (odds ratio [OR], .21; 95% CI, .07-.54) and unfavorable outcome (OR, 5.64; 95% CI, 1.80-18.58).Renal dysfunction (eGFR60 mL/minute/m(2)) was associated with poor clinical outcome after ICH.

Purpose: Atrial fibrillation (AF) is often detected after embolic events occur, and it is an obstacle to effective preventive anticoagulation. We aimed to determine a percentage of patients with nonvalvular AF (NVAF) unidentified prior to stroke in the overall stroke patients with NVAF, as well as background features, stroke severity and outcome of such occult NVAF patients. Methods: A total of 743 acute ischemic stroke/TIA patients with NVAF (344 women, 78±10 years old) were enrolled between Sep 2011 and Jun 2013 from a multicenter prospective registry (the SAMURAI-NVAF study, NCT01581502). Patients were divided into two groups; those with identified AF before stroke/TIA (Group I) and those with unidentified AF that was documented at emergent visit or later (Group U). Favorable outcome was defined as mRS 0-2 at hospital discharge (for 710 patients, median 23 days) and at 3 months (for 565 patients). Results: 285 patients belonged to the Group U (38%; 138 women, 78±11 years old). Although both median CHADS 2 (2 vs. 2, p2 DS 2 -VASc (3 vs. 4, p2 and 91% according to CHA 2 DS 2 -VASc in the Group U. After multivariate adjustment, paroxysmal AF (OR 1.91, 95% CI 1.24-2.75) was more common and congestive heart failure (0.63, 0.40-0.99) and premorbid use of oral anticoagulants (0.08, 0.04-0.13) were less common in the Group U than the Group I. The median initial NIHSS was higher in the Group U (11 [IQR 4-19]) than in the Group I (6 [2-17], p Conclusion: Two fifth of the stroke/TIA patients with NVAF were not diagnosed as having AF prior to the attack, though their ischemia-risk indices were generally high. Patients with such occult NVAF had severer stroke and worse outcome than those with identified AF.

Objective: Although intravenous thrombolysis (IVT) using alteplase for octogenarians with acute ischemic stroke becomes relatively familiar, it is unclear whether IVT for nonagenarians is a futile intervention. The purpose of this study is to clarify the efficacy and safety of IVT using low-dose alteplase (0.6 mg/kg) for nonagenarians compared with octogenarians. Methods: Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) rtPA registry retrospectively collected 600 consecutive acute stroke patients receiving IVT from 10 Japanese stroke centers between October 2005 and July 2008. We extracted all octogenarians (O group) and nonagenarians (N group) from the registry. We compared baseline characteristics, symptomatic intracranial hemorrhage (SICH), and 3-month outcomes between the groups. 3-month outcomes include; functional independence (FI) defined as a mRS score 0-2, good outcome (GO) as a mRS score 0-2 or same as the premorbid mRS, poor outcome (PO) defined as a mRS score 5-6, and death. Results: Twenty-five nonagenarians (mean age, 93 years) and 124 octogenarians (mean age, 84 years) were included. N group was more female-predominant (76% versus 56%, p=0.06) and premorbidly dependent (44% versus 14%, p Conclusions: IVT using low-dose alteplase for N group resulted in less frequent achievement of FI mainly because of more premorbid dependency than O group, however, showed at least a similar safety and a potential efficacy.

Purpose: Intravenous nicardipine is commonly used to reduce elevated blood pressure (BP) in acute intracerebral hemorrhage (ICH). We determined factors associated with nicardipine dose and the association of the dose with clinical outcomes in hyperacute ICH. Methods: Hyperacute (180 mmHg were registered in a multicenter observational study (the SAMURAI-ICH study). All patients initially received 5mg/h of intravenous nicardipine to lower BP. The dose was adjusted to maintain SBP between 120 and 160 mmHg based on BPs measured every 15 min during the initial 2 h and every 60 min in the following 22 h. Maximum hourly and total doses during the initial 24 h were calculated. Associations of the doses with neurological deterioration (a decrease of ≥2 in GCS or an increase of ≥4 in NIHSS score at 72 h after treatment initiation), hematoma expansion (>33% from baseline to 24 h), and unfavorable outcome (modified Rankin Scale score 4-6 at 3 months) were assessed. Results: Of 211 patients in the registry, 206 patients (81 women, 65.8±11.8 years old) whose nicardipine data were available throughout 24-h observation were studied. Initial BP was 201.9±15.9/107.9±15.1 mmHg. Median time to reach target SBP range was 30 min (IQR 15-45). Maximum and total doses were 9.1±4.2mg/h and 123.7±100.2mg/day, respectively. Multivariate analyses revealed that male sex [standardized regression coefficient (β)=0.20, p=0.0030 for maximum dose; β=0.25, p=0.0002 for total dose], age (β= -0.28, p=0.0002; β= -0.25, p=0.0005) and initial SBP (β=0.19, p=0.0018; β=0.18, p=0.0021) were independently associated with both maximum and total doses. Body weight (β=0.20, p=0.0084) was independently associated with total dose. After multivariate adjustment, maximum dose (per 1mg/h; OR 1.25, 95% CI 1.09-1.45; p=0.0022) was independently and total dose (per 10mg/day; OR 1.06, 95% CI 0.998-1.132; p=0.0555) tended to be associated with neurological deterioration. Nicardipine dose was not associated with hematoma expansion and unfavorable outcome. Conclusions: Nicardipine dosage is roughly predictable with sex, age, body weight and initial SBP in acute ICH. Maximum hourly nicardipine dose was associated with neurological deterioration.

BACKGROUND and PURPOSE: Blood pressure (BP) lowering may be beneficial for patients with hyperacute intracerebral hemorrhage (ICH). Although several trials including INTERACT 2 and ATACH II have a design of the strict BP lowering during the initial 24 hours, shorter duration may be enough since active bleeding may not last 24 hours. We aimed to examine the associations between sequential systolic BP levels during antihypertensive treatment (AHT) and clinical outcomes in acute ICH patients. METHODS: Hyperacute (180 mmHg were registered in a prospective, multicenter, observational study, the SAMURAI-ICH study (Koga J Hypertens 2012;30:2357). All patients received intravenous AHT, based on a predefined standardized protocol to lower and maintain SBP between 120 and 160 mmHg using intravenous nicardipine. BPs were measured hourly in the initial 24 hours. The mean of 8 SBP levels during 1 to 8, 9 to 16, and 17 to 24 hours after the initiation of AHT were calculated, and referred to as the 1st, 2nd and 3rd mSBPs, respectively. The associations between mSBPs and neurological deterioration (a decrease of ≥2 in GCS or an increase of ≥4 in NIHSS score), hematoma expansion (>33% in volume), and unfavorable outcome (modified Rankin Scale score 4-6 at 3 months) were assessed. RESULTS: 211 patients (81 women, median age 65 [IQR, 58-74] years, median initial NIHSS score 13 [8-17]) were included. The baseline hematoma volume was 10.2 (5.6-19.2) mL. Neurological deterioration was observed in 17 patients (8%), hematoma expansion in 36 (17%), and unfavorable outcome in 87 (41%). The 1st, 2nd, and 3rd mSBPs were 132 (126-138), 131 (125-140), and 137 (130-144) mmHg, respectively. The 1st (OR 2.41, 95%CI 1.34-4.69 per 10-mmHg) and 2nd mSBPs (2.08; 1.20-3.80) were independently associated with neurological deterioration (17 patients) and the 2nd (1.40; 1.02-2.00) and 3rd mSBPs (1.45; 1.05-2.05) were associated with unfavorable outcome (87 patients), although no mSBPs were associated with hematoma expansion (36 patients). CONCLUSIONS: Continuation of AHT throughout the initial 24 hours may ameliorate clinical outcomes.

Background and Purpose— A short duration ( Methods— In 211 hyperacute ICH patients who underwent AHT based on predefined protocol, the mean of hourly SBP (mSBP) measurements was calculated over 1 to 8 hours (first mSBP), 9 to 16 hours (second mSBP), and 17 to 24 hours (third mSBP) after the initiation of AHT. Outcomes included neurological deterioration (72-hour Glasgow Coma Scale decrease ≥2 or National Instititutes of Health Stroke Scale increase ≥4), hematoma expansion (>33%), and unfavorable outcome (3-month modified Rankin Scale score 4–6). Results— The median first, second, and third mSBPs were 132, 131, and 137 mm Hg, respectively. A higher first mSBP (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.34–4.69 per 10 mm Hg) or second mSBP (OR, 2.08; 95% CI, 1.20–3.80) was independently associated with neurological deterioration, and a higher second mSBP (OR, 1.40; 95% CI, 1.02–2.00) or third mSBP (OR, 1.45; 95% CI, 1.05–2.05) was associated with unfavorable outcome. None of the mSBPs was associated with hematoma expansion. Conclusions— The continuation of AHT throughout the initial 24 hours after ICH may improve outcomes.

The relationship between the features of MRI in brainstem and pathological findings was investigated in eight autopsy cases with progressive supranuclear palsy (PSP). Features of T1-weighted images at midbrain level were atrophy of tegmentum and tectum, and dilatation of aqueduct. Histologically, these findings were consistent with atrophy of periaqueductal gray matter, quadrigeminal plate, and tegmentum. In these lesions, we detected neuronal loss, decrease in density of myelinated fibers, gliosis, rarefaction of tissues, and tau-positive structures such as neurofibrillary tangles (NFTs), glial fibrillary tangles (GFTs) and neuropil threads. At pons level, atrophy of tegmentum, atrophy of pontine base, and dilatation of prepontine cistern were found. Tau-positive structures were observed not only in tegmentum but also in pontine base. The density of the tau-positive structure was closely related to the severity of atrophy. Features of T2-weighted images were high intensity in the periaqueductal lesion and tegmentum in pons. In these lesions, severe histological findings were detected. The MRI features in brainstem were closely related to the histological findings as PSP.

Background and Purpose— Blood pressure (BP) lowering is often conducted as part of general acute management in patients with acute intracerebral hemorrhage. However, the relationship between BP after antihypertensive therapy and clinical outcomes is not fully known. Methods— Hyperacute (180 mm Hg were included. All patients received intravenous antihypertensive treatment, based on predefined protocol to lower and maintain SBP between 120 and 160 mm Hg. BPs were measured every 15 minutes during the initial 2 hours and every 60 minutes in the next 22 hours (a total of 30 measurements). The mean achieved SBP was defined as the mean of 30 SBPs, and associations between the mean achieved SBP and neurological deterioration (≥2 points’ decrease in Glasgow Coma Score or ≥4 points’ increase in National Institutes of Health Stroke Scale score), hematoma expansion (>33% increase), and unfavorable outcome (modified Rankin Scale score 4–6 at 3 months) were assessed with multivariate logistic regression analyses. Results— Of the 211 patients (81 women, median age 65 [interquartile range, 58–74] years, and median initial National Institutes of Health Stroke Scale score 13 [8–17]) enrolled, 17 (8%) showed neurological deterioration, 36 (17%) showed hematoma expansion, and 87 (41%) had an unfavorable outcome. On multivariate regression analyses, mean achieved SBP was independently associated with neurological deterioration (odds ratio, 4.45; 95% confidence interval, 2.03–9.74 per 10 mm Hg increment), hematoma expansion (1.86; 1.09–3.16), and unfavorable outcome (2.03; 1.24–3.33) after adjusting for known predictive factors. Conclusions— High achieved SBP after standardized antihypertensive therapy in hyperacute intracerebral hemorrhage was independently associated with poor clinical outcomes. Aggressive antihypertensive treatment may ameliorate clinical outcomes.

Background and Purpose: Conjugate eye deviation (CED) occurs frequently in patients with acute stroke. The purpose of this study was to elucidate the factors that correlate with CED, as well as the relationship between CED and outcomes, in patients with acute intracerebral hemorrhage (ICH). Methods: A total of 211 patients with acute supratentorial ICH were recruited in a multicenter, prospective study. Both on admission and 72 hours later, CED was assessed with an NIH Stroke Scale “best gaze” subscore of ≥1. Hematoma location and volume were assessed on CT within 2.5 hours of onset. Results: Ninety-six (45%) patients had CED on admission. On multivariable analysis, right-sided lesion (OR 2.36, 95% CI 1.18-4.93), hematoma volume (OR 1.07, 95% CI 1.04-1.10 per 1 mL), and baseline GCS score (OR 0.66, 95% CI 0.53-0.80 per 1 point) were independently associated with CED. After adjusting for sex, age, intraventricular extension of the hematoma, baseline GCS score, and hematoma volume, the presence of CED both on admission and 72 hours later was an independent predictor of death or dependency at 3 months post-stroke (OR 5.77, 95% CI 2.27-16.94). The optimal cutoff volume of hematoma related to CED was ≥13.5 mL for patients with putaminal hemorrhage (sensitivity, 76%; specificity, 72%) and ≥7.7 mL for patients with thalamic hemorrhage (sensitivity, 82%; specificity, 83%). Conclusions: The persistence of CED was a significant predictor of death or dependency after acute supratentorial ICH even after adjusting for initial severity and hematoma volume. CED can be evoked by a relatively smaller thalamic hematoma than a putaminal hematoma. Bedside assessment of CED appears to provide valuable information related to chronic outcomes of patients with ICH.

Background and purpose: Characteristics of reverse MRA-DWI mismatch, defined as large DWI lesion despite absence of the major artery occlusion (MAO), remain unknown, especially in patients treated with IV rt-PA. This study aimed to clarify the frequency, associated factors, and outcomes of patients showing reverse MRA-DWI mismatch prior to IV rt-PA therapy. Methods: From the multicenter (SAMURAI) and additional single-center (NCVC) rt-PA registries, patients with the MCA territorial stroke were included. Early ischemic changes (EIC) were assessed with the Alberta Stroke Program Early CT score (ASPECTS) on pretreatment DWI. MAO was defined as ICA or M1 occlusion on MRA. Patients were divided into 4 groups: the large-EIC match (LM) group (MAO, ASPECTS Results: Of the 486 patients (167 women, median age 74 years) enrolled, reverse MRA-DWI mismatch was observed in 24 (5%, RMM group); 108 belonged to LM, 161 to CMM, and 193 to SM groups. Among clinical characteristics, cardioembolism (RMM 92%, LM 76%, CM 69%, SM 49%) was only independently associated with the RMM group (OR 5.49, 95%CI 1.25-24.1). Median initial NIHSS score was 18 in RMM, 18 in LM, 13 in CMM, and 8 in SM (p Conclusion: Reverse MRA-DWI mismatch was observed in 5% of patients eligible for rt-PA. Cardioembolism was independently associated with reverse mismatch. Patients with reverse mismatch may benefit from thrombolysis, compared to those with extensive EIC with MAO.

Background and Purpose— The present study determines associations between early blood pressure (BP) variability and stroke outcomes after intravenous thrombolysis. Methods— In 527 stroke patients receiving intravenous alteplase (0.6 mg/kg), BP was measured 8 times within the first 25 hours. BP variability was determined as ΔBP (maximum-minimum), standard deviation (SD), coefficient of variation, and successive variation. Results— The systolic BP course was lower among patients with modified Rankin Scale (mRS) 0 to 1 than those without ( P Conclusions— Early systolic BP variability was positively associated with symptomatic intracerebral hemorrhage and death after intravenous thrombolysis.

Background and Purpose— Conjugate eye deviation (CED) occurs frequently in patients with acute stroke. The purpose of this study was to elucidate the factors that correlate with CED as well as the relationship between CED and outcomes in patients with acute intracerebral hemorrhage. Methods— A total of 211 patients with acute supratentorial intracerebral hemorrhage were recruited in a multicenter, prospective study. CED was assessed with a National Institutes of Health Stroke Scale “best gaze” subscore of ≥1. Hematoma location and volume were assessed on CT. Results— Forty-five percent of the patients had CED. On multivariable analysis, right-sided lesion (OR, 2.36; 95% CI, 1.18–4.93), hematoma volume (OR, 1.07; 95% CI, 1.04–1.10 per 1 mL), and baseline Glasgow Coma Scale score (OR, 0.66; 95% CI, 0.53–0.80 per 1 point) were independently associated with CED. After adjusting for sex, age, intraventricular extension of the hematoma, baseline Glasgow Coma Scale score, and hematoma volume, the presence of CED both on admission and 72 hours later was an independent predictor of death or dependency at 3 months poststroke (OR, 5.77; 95% CI, 2.27–16.94). The optimal cutoff volume of hematoma related to CED was ≥13.5 mL for patients with putaminal hemorrhage (sensitivity, 76%; specificity, 72%) and ≥7.7 mL for patients with thalamic hemorrhage (sensitivity, 82%; specificity, 83%). Conclusions— The persistence of CED was a significant predictor of death or dependency after acute supratentorial intracerebral hemorrhage even after adjusting for initial severity and hematoma volume. CED can be evoked by a relatively smaller thalamic hematoma than a putaminal hematoma.

Purpose The aim of this study was to examine whether CHADS 2 score is associated with clinical outcomes following recombinant tissue type plasminogen activator (rt-PA) therapy in stroke patients with atrial fibrillation (AF). Methods We studied 218 consecutive stroke patients with AF [126 men, mean age 74.2 (SD 9.6) years] who received intravenous rt-PA therapy. CHADS 2 score was calculated as follows: 2 points for prior ischemic stroke and 1 point for each of the following: age ≥ 75 years, hypertension, diabetes, and congestive heart failure. Results Congestive heart failure was documented in 23 patients, hypertension in 138, age ≥ 75 years in 116, diabetes in 35, and prior stroke in 35. The distribution of each CHADS 2 score was: score of 0, 16.1% of patients; 1, 30.3%; 2, 29.4%; and 3 to 5, 24.3%. The median initial NIHSS score for each CHADS 2 category was 12 (IQR 8–17), 16 (10–20), 14.5 (10–20.75), and 16 (11–21), respectively ( p = 0.168). Symptomatic ICH within the initial 36 h was found in 2.9%, 4.6%, 6.3%, and 0% of patients with each CHADS 2 category, respectively. Cardiovascular events within 3 months occurred in 0%, 0%, 7.8% and 5.7%, respectively. Percentage of patients with chronic independence at 3 months corresponding to modified Rankin Scale ≤ 2 was 57.1%, 45.5%, 31.3%, and 28.3%, respectively. Adjusted CHADS 2 score was inversely associated with chronic independence (OR 0.72, 95% CI 0.55–0.93). Conclusion Lower CHADS 2 score was associated with chronic independence at 3 months after intravenous rt-PA therapy in stroke patients with AF.

We evaluated whether pre- and post-stroke statin use was associated with intracranial hemorrhage (ICH) and clinical outcome at 3 months after intravenous recombinant tissue plasminogen activator (IV rt-PA) for acute ischemic stroke.This study enrolled 600 consecutive patients (72 +/- 12 years, woman 37.2%) who received IV rt-PA at ten stroke centers that participated in the SAMURAI rt-PA Registry from October 2005 to July 2008.Statins were used prior to stroke in 112% and within 72 h after IV rt-PA in 10.0% of patients. One hundred nineteen patients (19.8%) developed ICH. Pre-stroke statin use was not an independent factor associated with ICH (OR 1.46; 95% CI 0.76-2.81, p = 0.225). Of 535 patients with a premorbid mRSor = 1, 199 (37.2%) had a favorable clinical outcome at 3 months (mRSor = 1). Pre-stroke statin use (OR 1.05; 95% CI 0.55-2.01, p = 0.879), as well as post-stroke statin use (OR 1.31; 95% CI 0.66-2.59, p = 0.440), was not an independent predictor of outcome.In patients who received IV rt-PA for acute ischemic stroke, statin use did not increase ICH after thrombolysis, nor was it associated with clinical outcome.

Background: The aim of this study was to determine whether renal dysfunction affects the outcome of stroke patients treated with recombinant tissue plasminogen activator (rt-PA). Methods: A retrospective, multicenter, observational study was conducted to identify the effects of underlying risk factors on intravenous rt-PA therapy using 0.6 mg/kg alteplase in 10 stroke centers in Japan. Consecutive stroke patients with a premorbid modified Rankin Scale (mRS) score ≤3 who received rt-PA were studied. Renal dysfunction was defined as estimated glomerular filtration rate (eGFR) 2 on admission. The outcome measures were any intracerebral hemorrhage (ICH) and symptomatic ICH within the initial 36 h; favorable (mRS 0–1) outcome, poor outcome (mRS 4–6) and mortality at 3 months. Results: Of a total of 578 patients (372 men; 64.4%, 71.4 ± 11.7 years old), renal dysfunction was present in 186 patients (32.2%). These patients were older and more commonly had hypertension, atrial fibrillation, prior ischemic heart disease and prior use of antithrombotic agents than patients without renal dysfunction. ICH (27.4 vs. 16.6%) and symptomatic ICH (8.1 vs. 2.6%) was more common in patients with renal dysfunction than in those without. At 3 months, patients with renal dysfunction had higher median mRS scores than those without (3 vs. 2). After multivariate adjustment for established outcome predictors, renal dysfunction was related to any ICH (odds ratio 1.81, 95% confidence interval 1.16–2.84), symptomatic ICH (2.64, 1.10–6.56), poor outcome (1.55, 1.01–2.38), and mortality (2.94, 1.38–6.42). Conclusions: Reduced eGFR was associated with early ICH and 3-month unfavorable outcome in stroke patients receiving intravenous rt-PA.